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PR00945

Identifier
HGRDTASE  [View Relations]  [View Alignment]  
Accession
PR00945
No. of Motifs
8
Creation Date
27-JUL-1998  (UPDATE 20-JUN-1999)
Title
Mercuric reductase class II signature
Database References

PROSITE; PS01047 HMA
BLOCKS; BL01047
INTERPRO; IPR000815
UMBBD; e0056
PDB; 1AFI; 1AFJ
SCOP; 1AFI; 1AFJ
Literature References
1. BULL, P.C. AND COX, D.W. 
Wilson disease and Menkes disease - new handles on heavy-metal transport.
TRENDS GENET. 10 246-252 (1994).
 
2. STEELE, R.A. AND OPELLA, S.J.
Structures of the reduced and mercury-bound forms of MerP, the periplasmic
protein from the bacterial mercury detoxification system. 
BIOCHEMISTRY 36 6885-6895 (1997). 

Documentation
Proteins that transport heavy metals in micro-organisms and mammals share
similarities in their sequences and structures. These proteins provide an
important focus for research, some being involved in bacterial resistance
to toxic metals, such as lead and cadmium, while others are involved in
inherited human syndromes, such as Wilson and Menkes diseases [1].
 
A conserved 30-residue domain has been found in a number of these heavy
metal transport or detoxification proteins [1]. The domain, which has been
termed Heavy-Metal-Associated (HMA), contains two conserved cysteines that
are probably involved in metal binding. 
 
The HMA domain has been identified in the N-terminal regions of a variety
of cation transporting ATPases, and in other ATPases such as fixI from 
Rhizobium meliloti; pacS from Synechococcus strain PCC 7942; Mycobacterium 
leprae ctpA and ctpB; and Escherichia coli hypothetical protein yhhO. In
addition, the domain has been found in bacterial mercuric reductase; the
copP copper-binding protein of Helicobacter pylori; and in the N-terminal 
regions of mercuric transport protein periplasmic component (gene merP) and
plasmids carried by mercury-resistant Gram-negative bacteria, where it seems
to be a mercury scavenger that specifically binds to one Hg(2+) ion, passing
this to mercuric reductase via the merT protein. 
 
The structure of the mercuric ion-binding protein MerP from Shigella
flexneri has been determined. The fold has been classed as a ferredoxin-like
alpha-beta sandwich, having a beta-alpha beta-beta alpha-beta architecture,
with the two alpha-helices overlaying a four-stranded anti-parallel beta-
sheet [2]. Structural differences between the reduced and mercury-bound 
forms of merP are localised to the metal-binding loop containing the 
consensus sequence GMTCXXC, the two cysteines of which are involved in
bi-coordination of Hg(2+) [2].
 
Mercuric reductase, which contains a single copy of the HMA domain, is
involved in a specialised system that confers resistance to Hg(2+) on 
bacteria. The merA protein is responsible for volatilising mercury, 
catalysing the reaction:
 
 Hg + NADP(+) + H(+) = Hg(2+) + NADPH
 
The protein functions as a homodimer, with an FAD flavoprotein; its active
site is a redox-active disulphide bond. 
 
HGRDTASE is an 8-element fingerprint that provides a signature for class II
mercuric reductases. The fingerprint was derived from an initial alignment
of 5 sequences: the motifs were drawn from conserved regions spanning
the N-terminal half of the alignment - motif 1, which lies in the HMA 
domain, encodes the first alpha-helix, and includes the second metal-
binding cysteine; and motif 2 lies in the putative FAD binding domain. 
Two iterations on OWL30.2 were required to reach convergence, at which 
point a true set comprising 19 sequences was identified. Several partial 
matches were also found, all of which are mercuric reductases or related 
enzymes that fail to match one or more motifs. 
 
An update on SPTR37_9f identified a true set of 19 sequences, and 11
partial matches.
Summary Information
  19 codes involving  8 elements
0 codes involving 7 elements
0 codes involving 6 elements
2 codes involving 5 elements
0 codes involving 4 elements
1 codes involving 3 elements
8 codes involving 2 elements
Composite Feature Index
81919191919191919
700000000
600000000
501122211
400000000
300011001
202145130
12345678
True Positives
MERA_ACICA    MERA_ALCSP    MERA_BACSR    MERA_ENTAG    
MERA_PSEAE MERA_PSEFL MERA_SHEPU MERA_SHIFL
MERA_STAAU MERA_THIFE O05610 O06510
O08449 O54319 O66017 O69236
O69256 O86216 Q56447
True Positive Partials
Codes involving 5 elements
MERA_STRLI Q56283
Codes involving 3 elements
P73059
Codes involving 2 elements
DLD1_BACST DLD1_BACSU GSHR_PSEAE O13631
P96104 Q56285 Q60151 YKGC_ECOLI
Sequence Titles
MERA_ACICA  MERCURIC REDUCTASE (EC 1.16.1.1) (HG(II) REDUCTASE) - ACINETOBACTER CALCOACETICUS. 
MERA_ALCSP MERCURIC REDUCTASE (EC 1.16.1.1) (HG(II) REDUCTASE) - ALCALIGENES SP.
MERA_BACSR MERCURIC REDUCTASE (EC 1.16.1.1) (HG(II) REDUCTASE) - BACILLUS SP. (STRAIN RC607).
MERA_ENTAG MERCURIC REDUCTASE (EC 1.16.1.1) (HG(II) REDUCTASE) - ENTEROBACTER AGGLOMERANS.
MERA_PSEAE MERCURIC REDUCTASE (EC 1.16.1.1) (HG(II) REDUCTASE) - PSEUDOMONAS AERUGINOSA.
MERA_PSEFL MERCURIC REDUCTASE (EC 1.16.1.1) (HG(II) REDUCTASE) - PSEUDOMONAS FLUORESCENS.
MERA_SHEPU MERCURIC REDUCTASE (EC 1.16.1.1) (HG(II) REDUCTASE) - SHEWANELLA PUTREFACIENS (PSEUDOMONAS PUTREFACIENS).
MERA_SHIFL MERCURIC REDUCTASE (EC 1.16.1.1) (HG(II) REDUCTASE) - SHIGELLA FLEXNERI.
MERA_STAAU MERCURIC REDUCTASE (EC 1.16.1.1) (HG(II) REDUCTASE) - STAPHYLOCOCCUS AUREUS.
MERA_THIFE MERCURIC REDUCTASE (EC 1.16.1.1) (HG(II) REDUCTASE) - THIOBACILLUS FERROOXIDANS.
O05610 MERCURIC ION REDUCTASE - PSEUDOMONAS SP.
O06510 MERCURIC REDUCTASE - ENTEROBACTER CLOACAE.
O08449 MERCURIC REDUCTASE (EC 1.16.1.1) (MERCURY (II) REDUCTASE) - PSEUDOMONAS SP.
O54319 MERCURIC REDUCTASE - THIOBACILLUS SP.
O66017 MERA - PSEUDOMONAS STUTZERI (PSEUDOMONAS PERFECTOMARINA).
O69236 MERCURIC REDUCTASE - BACILLUS CEREUS.
O69256 MERCURIC REDUCTASE - BACILLUS MEGATERIUM.
O86216 MERCURIC REDUCTASE - EXIGUOBACTERIUM SP.
Q56447 MERCURIC REDUCTASE (EC 1.16.1.1) (HG(II) REDUCTASE) - UNIDENTIFIED.

MERA_STRLI MERCURIC REDUCTASE (EC 1.16.1.1) (HG(II) REDUCTASE) - STREPTOMYCES LIVIDANS.
Q56283 ORF-1 - THIOBACILLUS FERROOXIDANS.

P73059 MERCURIC REDUCTASE - SYNECHOCYSTIS SP. (STRAIN PCC 6803).

DLD1_BACST DIHYDROLIPOAMIDE DEHYDROGENASE (EC 1.8.1.4) (E3 COMPONENT OF PYRUVATE COMPLEX) - BACILLUS STEAROTHERMOPHILUS.
DLD1_BACSU DIHYDROLIPOAMIDE DEHYDROGENASE (EC 1.8.1.4) (E3 COMPONENT OF PYRUVATE COMPLEX) (S COMPLEX, 50 KD SUBUNIT) - BACILLUS SUBTILIS.
GSHR_PSEAE GLUTATHIONE REDUCTASE (EC 1.6.4.2) (GR) (GRASE) - PSEUDOMONAS AERUGINOSA.
O13631 GLUTATHIONE REDUCTASE - SCHIZOSACCHAROMYCES POMBE (FISSION YEAST).
P96104 DIHYDROLIPOYL TRANSACETYLASE AND LIPOAMIDE DEHYDROGENASE OF THE PYRUVATE DEHYDROGENASE COMPLEX - THIOBACILLUS FERROOXIDANS.
Q56285 ORF-3 - THIOBACILLUS FERROOXIDANS.
Q60151 GLUTATHIONE REDUCTASE (EC 1.6.4.2) (GLUTATHIONE REDUCTASE (NADPH)) - STREPTOCOCCUS THERMOPHILUS.
YKGC_ECOLI PROBABLE PYRIDINE NUCLEOTIDE-DISULFIDE OXIDOREDUCTASE IN EAEH-BETA INTERGENIC REGION - ESCHERICHIA COLI.
Scan History
OWL30_2    2  100  NSINGLE    
SPTR37_9f 2 50 NSINGLE
Initial Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
SCATHVKDALE MERA_ALCSP 12 12 -
GCEEHVTEALE MERA_STAAU 17 17 -
SCAAHVKEALE MERA_SERMA 13 13 -
SCVAHVKEALD MERA_PSEPT 13 13 -
SCAVHAQQTLE TST32MER3 16 16 -

Motif 2 width=19
Element Seqn Id St Int Rpt
AMAAALKAVEQGANVTLIE MERA_ALCSP 108 85 -
AMAAALKAVEQGARVTLIE TST32MER3 111 84 -
AMAAALKAVEQGAQVTLIE MERA_SERMA 110 86 -
AFACAIKAAEGGAKVTLIE MERA_PSEPT 106 82 -
AFSAAIKANENGAKVAMVE MERA_STAAU 97 69 -

Motif 3 width=20
Element Seqn Id St Int Rpt
KIMIRAAHIAHLRRESPFDG MERA_ALCSP 143 16 -
KIMIRAAHIAHLRRESPFDG MERA_SERMA 145 16 -
KILIRAAQLAQQQRNNPFTG MERA_PSEPT 142 17 -
KIMIRAAHIAHLRQESPFDG TST32MER3 146 16 -
KTMLRAGEINGLAQNNPFTG MERA_STAAU 132 16 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LVATGASPAVPPIPGLKE MERA_ALCSP 235 72 -
LIATGASPAVPEIPGMNE MERA_STAAU 217 65 -
LVATGASPAMPPIPGLKE MERA_SERMA 237 72 -
LIATGSTPTIPPIDGLTE MERA_PSEPT 233 71 -
LIATGASPAIPPIPGLKD TST32MER3 238 72 -

Motif 5 width=18
Element Seqn Id St Int Rpt
RLAVIGSGYIAAELGQMF MERA_STAAU 252 17 -
RLAVIGSSVVALELAQAF TST32MER3 273 17 -
HLVVIGSSVVALEIAQAY MERA_PSEPT 268 17 -
RLAVIGSSVVALELAQAF MERA_SERMA 272 17 -
RLAVIGSSVVALELAQAF MERA_ALCSP 270 17 -

Motif 6 width=16
Element Seqn Id St Int Rpt
LGSQVTILARNTLFFR MERA_SERMA 292 2 -
LGTEVTLMQRSERLFK MERA_STAAU 272 2 -
LGSKVTILARSTLFFR MERA_ALCSP 290 2 -
LGSEVTILARHTLLYR MERA_PSEPT 288 2 -
LGSQVTILARGTLFLR TST32MER3 293 2 -

Motif 7 width=21
Element Seqn Id St Int Rpt
LTLDNVPRALANFDTRGFIKL TST32MER3 470 161 -
LTLDNVPRALANFDTRGFIKL MERA_SERMA 368 60 -
LEMENVPRALANFETDGFIKL MERA_PSEPT 465 161 -
LTLDNVPRALANFDTRGFIKL MERA_ALCSP 467 161 -
LPLDAVPRALVNHETTGVYKL MERA_STAAU 455 167 -

Motif 8 width=20
Element Seqn Id St Int Rpt
PYLTMVEGLKLAAQTFTKDV MERA_SERMA 433 44 -
PYLTMVEGLKLAAQTFSKDV MERA_ALCSP 532 44 -
PYLTMAEGLKLAALTFDKDV MERA_STAAU 520 44 -
PYLTMVEGIKLCAQTFTRDV TST32MER3 535 44 -
PYLTMVEGLKLCAQTFNKDV MERA_PSEPT 530 44 -
Final Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
SCAAHVKEALE MERA_PSEAE 13 13 -
SCATHVKDALE MERA_PSEFL 13 13 -
SCATHVKDALE MERA_ALCSP 12 12 -
SCAAHVKEALE MERA_ACICA 13 13 -
SCATHVKDALE Q56447 13 13 -
SCAAHVKEALE O06510 13 13 -
SCAAHVKEALE MERA_ENTAG 13 13 -
SCAGHVKEALE O66017 13 13 -
SCAVHVKDALE MERA_SHIFL 13 13 -
GCAAHVRKALE MERA_THIFE 18 18 -
SCVVHVKEALE O05610 13 13 -
SCAVHAQQTLE O54319 16 16 -
SCTRHVEDALL O08449 18 18 -
SCVAHVKEALD MERA_SHEPU 13 13 -
GCEEHVAVALE O69236 15 15 -
GCEEHVTEALE MERA_STAAU 17 17 -
GCEEHVAVALE O69256 94 94 -
GCEQHVAVALE MERA_BACSR 15 15 -
GCEQHVAVALE O86216 15 15 -

Motif 2 width=19
Element Seqn Id St Int Rpt
AMAAALKAVEQGAQVTLIE MERA_PSEAE 110 86 -
AMAAALKAVEQGATVTLIE MERA_PSEFL 97 73 -
AMAAALKAVEQGANVTLIE MERA_ALCSP 108 85 -
AMAAALKAVEQGAHVSLIE MERA_ACICA 110 86 -
AMAAALKAVEQGATVTLIE Q56447 97 73 -
AMAAALKAVEQGAQVTLIE O06510 110 86 -
AMAAALKAVEQGAQVTLIE MERA_ENTAG 110 86 -
AMAAALKAVEQGAQVTLIE O66017 110 86 -
AMAAALKAVEQGARVTLIE MERA_SHIFL 109 85 -
AMACALKAVERGARVTLIE MERA_THIFE 96 67 -
AMAAALKVVEGGARVTLIE O05610 108 84 -
AMAAALKAVEQGARVTLIE O54319 111 84 -
AVAAALKAAENGARFTLIE O08449 118 89 -
AFACAIKAAEGGAKVTLIE MERA_SHEPU 106 82 -
AFSSAIEAVKYGAKVAMIE O69236 96 70 -
AFSAAIKANENGAKVAMVE MERA_STAAU 97 69 -
AFSSAIEAVALNAKVAMIE O69256 181 76 -
AFSSAIEAVALNAKVAMIE MERA_BACSR 181 155 -
AFSSAIEAVALNAKVAMIE O86216 181 155 -

Motif 3 width=20
Element Seqn Id St Int Rpt
KIMIRAAHIAHLRRESPFDG MERA_PSEAE 145 16 -
KIMIRAAHIAHLRRESPFDG MERA_PSEFL 132 16 -
KIMIRAAHIAHLRRESPFDG MERA_ALCSP 143 16 -
KIMIRAAHIAHLRRESPFDG MERA_ACICA 145 16 -
KIMIRAAHIAHLRRESPFDG Q56447 132 16 -
KIMIRVAHIAHLRRESPFDG O06510 145 16 -
KIMIRVAHIAHLRRESPFDG MERA_ENTAG 145 16 -
KIMIRAAHIAHLRRESPFDG O66017 145 16 -
KIMIRAAHIAHLRRESPFDG MERA_SHIFL 144 16 -
KIMIRAAHIAHLRRESPFDG MERA_THIFE 131 16 -
KIMIRAAHVAHLRRESPFDA O05610 143 16 -
KIMIRAAHIAHLRQESPFDG O54319 146 16 -
KIMIRAAHIAHLRRESPFDV O08449 153 16 -
KILIRAAQLAQQQRNNPFTG MERA_SHEPU 142 17 -
KTLLRAGEINHLAKNNPFVG O69236 131 16 -
KTMLRAGEINGLAQNNPFTG MERA_STAAU 132 16 -
KTLLRAGEINHLAKNNPFVG O69256 216 16 -
KTLLRAGEINHLAKNNPFVG MERA_BACSR 216 16 -
KTLLRAGEINHLAKNNPFVG O86216 216 16 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LVATGASPAVPPIPGLKE MERA_PSEAE 237 72 -
LVATGASPAVPPIPGLKE MERA_PSEFL 224 72 -
LVATGASPAVPPIPGLKE MERA_ALCSP 235 72 -
LVATGASPAVPPIPGLKE MERA_ACICA 237 72 -
LVATGASPVVPPIPGLKE Q56447 224 72 -
LVATGASPAVPPIPGLKE O06510 237 72 -
LVATGASPAVPPIPGLKE MERA_ENTAG 237 72 -
LVATGASPAVPPIPGLKE O66017 237 72 -
LIATGASPAVPPIPGLKD MERA_SHIFL 236 72 -
LVATGASPAVPPIPGLKD MERA_THIFE 223 72 -
LVATGASAAVPPIPGLKD O05610 235 72 -
LIATGASPAIPPIPGLKD O54319 238 72 -
LIATGASAAIPPLPGLAG O08449 245 72 -
LIATGSTPTIPPIDGLTE MERA_SHEPU 233 71 -
LIATGASPAKPNIPGLNE O69236 216 65 -
LIATGASPAVPEIPGMNE MERA_STAAU 217 65 -
LIATGASSTAPNIPGLDE O69256 301 65 -
LIATGASSTAPNIPGLDE MERA_BACSR 301 65 -
LIATGASSTAPNIPGLDE O86216 301 65 -

Motif 5 width=18
Element Seqn Id St Int Rpt
RLAVIGSSVVALELAQAF MERA_PSEAE 272 17 -
RLAVIGSSVVALELAQAF MERA_PSEFL 259 17 -
RLAVIGSSVVALELAQAF MERA_ALCSP 270 17 -
RLAVIGSSVVALELAQAF MERA_ACICA 272 17 -
RLAVIGSSVVALELAQAF Q56447 259 17 -
RLAVIGSSVVALELAQAF O06510 272 17 -
RLAVIGSSVVALELAQAF MERA_ENTAG 272 17 -
PLAVIGSSVVALELAQAF O66017 272 17 -
RLAVIGSSVVALELAQAF MERA_SHIFL 271 17 -
RLAVIGSSVVALELAQAF MERA_THIFE 258 17 -
RLAVIGASVVAVELAQAF O05610 270 17 -
RLAVIGSSVVALELAQAF O54319 273 17 -
RLAVIGASVVALELAQAF O08449 280 17 -
HLVVIGSSVVALEIAQAY MERA_SHEPU 268 17 -
RLVVIGSGYIGMELGQLF O69236 251 17 -
RLAVIGSGYIAAELGQMF MERA_STAAU 252 17 -
RLTVIGSGYIGMELGQLF O69256 336 17 -
RLTVIGSGYIGMELGQLF MERA_BACSR 336 17 -
RLTVIGSGYIGMELGQLF O86216 336 17 -

Motif 6 width=16
Element Seqn Id St Int Rpt
LGSKVTVLARNTLFFR MERA_PSEAE 292 2 -
LGSQVTILARSTLFFR MERA_PSEFL 279 2 -
LGSKVTILARSTLFFR MERA_ALCSP 290 2 -
LGSQVTILARNTLFFR MERA_ACICA 292 2 -
LGSQVTILARSTLFFR Q56447 279 2 -
LGSKVTALARNTLFFR O06510 292 2 -
LGSKVTALARNTLFFR MERA_ENTAG 292 2 -
LGSKVTVLARNTLFFR O66017 292 2 -
LGAKVTILARSTLFFR MERA_SHIFL 291 2 -
LGSHVTILARGTLFLR MERA_THIFE 278 2 -
LGSEVTILARSAMFFH O05610 290 2 -
LGSQVTILARGTLFLR O54319 293 2 -
LGSEVTVLARRTLFAS O08449 300 2 -
LGSEVTILARHTLLYR MERA_SHEPU 288 2 -
LGSEVTLIQRSERLLK O69236 271 2 -
LGTEVTLMQRSERLFK MERA_STAAU 272 2 -
LGSEVTLIQRSERLLK O69256 356 2 -
LGSEVTLIQRSERLLK MERA_BACSR 356 2 -
LGSEVTLIQRSERLLK O86216 356 2 -

Motif 7 width=21
Element Seqn Id St Int Rpt
LTLDNVPRALANFDTRGFIKL MERA_PSEAE 469 161 -
LTLDNVPRALANFDTRGFIKL MERA_PSEFL 456 161 -
LTLDNVPRALANFDTRGFIKL MERA_ALCSP 467 161 -
LTLDNVPRALANFDTRGFIKL MERA_ACICA 469 161 -
LTLDNVPRALANFDTRGFIKL Q56447 456 161 -
LTLDNVPRALANFDTRGFIKL O06510 469 161 -
LTLDNVPRALANFDTRGFIKL MERA_ENTAG 469 161 -
LTLDNVPRALANFDTRGFIKL O66017 469 161 -
LTLDNVPRALANFDTRGFIKL MERA_SHIFL 472 165 -
MTLDNVPRALANFNTRGFIKL MERA_THIFE 453 159 -
LTLDNVPRALANFDTRGFIKL O05610 467 161 -
LTLDNVPRALANFDTRGFIKL O54319 470 161 -
LTLDNVPRALANFDTRGFIKL O08449 477 161 -
LEMENVPRALANFETDGFIKL MERA_SHEPU 465 161 -
LPLDAVPRALVNRETTGVFKL O69236 454 167 -
LPLDAVPRALVNHETTGVYKL MERA_STAAU 455 167 -
LPLDAVPRALVNRETTGVFKL O69256 539 167 -
LPLDAVPRALVNRETTGVFKL MERA_BACSR 539 167 -
LPLDAVPRALVNRETTGVFKL O86216 539 167 -

Motif 8 width=20
Element Seqn Id St Int Rpt
PYLTMVEGLKLAAQTFNKDV MERA_PSEAE 534 44 -
PYLTMVEGLKLAAQTFNKDV MERA_PSEFL 521 44 -
PYLTMVEGLKLAAQTFSKDV MERA_ALCSP 532 44 -
PYLTMVEGLKLAAQTFSKDV MERA_ACICA 534 44 -
PYLTMVEGLKLAAQTFNKDV Q56447 521 44 -
PYLTMVEGLKLAAQTFSKDV O06510 534 44 -
PYLTMVEGLKLAAQTFSKDV MERA_ENTAG 534 44 -
PYLTMVEGLKLAAQTFNKDV O66017 534 44 -
PYLTMVEGLKLAAQTFNKDV MERA_SHIFL 537 44 -
PYLTMVEGLKLAAQTFTRDV MERA_THIFE 518 44 -
PYLTMVEGLKLAAQTFNKDV O05610 532 44 -
PYLTMVEGIKLCAQTFTRDV O54319 535 44 -
PYLTMVQGLKLVAQTFSKDV O08449 542 44 -
PYLTMVEGLKLCAQTFNKDV MERA_SHEPU 530 44 -
PYLTMAEGLKLAALTFDKDI O69236 519 44 -
PYLTMAEGLKLAALTFDKDV MERA_STAAU 520 44 -
PYLTMAEGLKLAALTFDKDV O69256 604 44 -
PYLTMAEGLKLAVLTFDKDV MERA_BACSR 604 44 -
PYLTMAEGLKLAVLTFDKDV O86216 604 44 -